antihypertensive agents 1
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antihypertensive agents 1
- 2. Antihypertensive Agents By M. H. Farjoo MD , PhD Shahid Beheshti University of Medical Science
- 3. Antihypertensive Agents Classification Diuretics Sympathoplegic agents Direct vasodilators Angiotensin Blockers Hypertensive Emergencies Drug Pictures
- 4. Anatomic sites of blood pressure control
- 5. Sites of action of antihypertensive drugs
- 8. Diuretics The diuretics most important for treating hypertension are the thiazides and the loop diuretics. Thiazides are used in mild and moderate hypertension Loop agents are used in severe hypertension and in hypertensive emergencies. Compensatory responses to blood pressure lowering by diuretics are minimal. With thiazides, the antihypertensive effect is achieved with doses lower than their diuretic effect.
- 9. Compensatory responses are significant for some of these agents. Drugs are classified according to the site at which they impair the sympathetic reflex arc: Act on the CNS Ganglion blockers Reduce norepinephrine release Block adrenoceptors Sympathoplegic agents Cause inhibition of ejaculation, and orthostatic hypotension (not in use) Produce autonomic instability (not in use) May cause sedation, depression, nightmares (Methyldopa, Clonidine) Side effects is according to the receptor to which they bind.
- 11. Methyldopa, Clonidine They cause a decrease in sympathetic outflow by activation of α2 receptors in the CNS. Methyldopa may protect kidney function and was safe in pregnancy. It is sometimes preferred for hypertension in pregnancy.
- 12. Alpha1 Blockers Prazosin, terazosin, and doxazosin selectively block α1 receptors in arterioles and venules. These agents produce less reflex tachycardia and little postural hypotension. Alpha1 selectivity allows norepinephrine to exert unopposed negative feedback. A precipitous drop in standing blood pressure develops after the first dose (first-dose phenomenon). The first dose should be small and should be administered at bedtime.
- 14. β Adrenoceptor Antagonists Propranolol is the prototype, and atenolol, metoprolol, and carvedilol are among the most popular. β blockers reduce renin release from the kidney. Because of lower lipid solubility, β1-selective blockers have fewer CNS effects.
- 15. Vasodilators
- 16. They consist of: Oral: hydralazine (for outpatient) and minoxidil (for sever hypertension) Parenteral : nitroprusside, diazoxide, and fenoldopam. The calcium channel blockers. All of the vasodilators relax arterioles, sodium nitroprusside also relaxes veins. Vasodilators Used to treat severe hypertention Used in both circumstances.
- 17. Sodium Nitroprusside The release of nitric oxide (from the drug molecule itself) stimulates guanylyl cyclase and increases cGMP. It rapidly lowers blood pressure, and its effects disappear within 1-10 minutes after discontinuation. So it must be infused continuously. It is light-sensitive, and must be made up fresh and covered with opaque foil.
- 18. Diazoxide Diazoxide is given as IV boluses or as an infusion and has several hours’ duration of action. This drug also reduces insulin release and can be used to treat hypoglycemia caused by insulin-producing tumors.
- 19. Fenoldopam Fenoldopam causes prompt, marked arteriolar vasodilation. This drug is given by IV infusion and has a short duration of action (10 min). It is administered by continuous IV infusion.
- 20. Calcium Channel Blockers (CCBs) Nifedipine is more selective as a vasodilator and have less cardiac depressant effect. Verapamil has the greatest depressant effect on the heart. It is recommended that nifedipine not be used for hypertension. CCBs with long half-lives are more appropriate for chronic hypertension.
- 22. Inhibitors of Angiotensin (cont’d) Even in low-renin hypertensive states, these drugs can lower blood pressure. Two classes of drugs act on the renin- angiotensin system: The ACE inhibitors The inhibitors of angiotensin at its receptors (ARB).
- 23. ACE Inhibitors They consist of Captopril, Enalapril and Lisinopril. They are also useful in heart failure and diabetes. Their toxicities include cough (30%), hyperkalemia, and renal damage, but protect the diabetic kidney. They cause major renal damage in the fetus and are absolutely contraindicated in pregnancy. Severe hypotension can occur after initial doses of any ACE inhibitor (first dose phenomenon).
- 24. Angiotensin Receptor Blockers They consist of losartan and valsartan. They competitively inhibit angiotensin II at its AT1 receptor site. ARBs effectiveness is similar to ACE inhibitors but have a lower incidence of cough. Like the ACE inhibitors, they do cause hyperkalemia. They also cause fetal renal toxicity and are thus contraindicated in pregnancy.
- 25. Hypertensive Emergencies They occur in poorly controlled patients or those who suddenly discontinue the drug. Hypertensive emergencies include hypertension with vascular damage (formerly: malignant hypertension). Hypertensive encephalopathy is a classic feature of malignant hypertension. It consists of: severe headache, mental confusion, blurred vision, vomiting, and focal neurologic deficits. If untreated, the syndrome progresses in 12-48 hours to convulsions, coma, and death.
- 27. Hypertensive Emergencies (cont’d) Parenteral drugs are used to lower blood pressure rapidly (within a few hours). Powerful vasodilators (nitroprusside, fenoldopam, or diazoxide) are combined with furosemide and β blockers Further reduction is then pursued more slowly.
- 36. Hydralazine
- 41. Propranolol tablet 10 mg Price of each pack (100 tablet): 4,500 Toman
- 42. Propranolol tablet 20 mg Price of each pack (100 tablet): 5,000 Toman
- 43. Propranolol tablet 40 mg Price of each pack (100 tablet): 6,000 Toman
- 44. Propranolol ampule 1 mg/1 ml Price of each pack: ??? Toman
- 45. Metoprolol tablet 50 mg Price of each package (30 tablets) 2,200 Toman
- 46. Metoprolol tablet 50 mg Price of each package (30 tablets) 2,200 Toman
- 47. Metoprolol tablet 50 mg Price of each package (100 tablets) 7,200 Toman
- 48. carvedilol tablet 6.25 mg Price of each package (100 tablets) 10,000 Toman
- 49. carvedilol tablet 6.25 mg Price of each package (30 tablets) 3,150 Toman
- 50. Carvedilol tablet 12.5 mg Price of each package (100 tablets) 12,500 Toman
- 51. carvedilol tablet 25 mg Price of each package (30 tablets) 7,200 Toman
- 53. Nifedipine
- 54. Nimodipine
- 57. Verapamil tablet 40 mg Price of each pack: 7,000 Toman
- 58. Verapamil ampule 5 mg / 2 ml Price of each ampule: 3,500 Toman
- 59. Diltiazem tab 60 mg Price of each pack (100 tablets): 13,000 Toman
- 60. Diltiazem 120 mg Price of each pack: 17,000 Toman
- 65. Diazoxide capsule 25 mg Price of each pack: ??? Toman
- 66. Diazoxide tablet 50 mg Price of each pack: 460,000 Toman Price of each single tablet: 4,600 Toman
- 67. Diazoxide capsule 100 mg Price of each pack: 630,000 Toman Price of each single capsule: 6,300 Toman
- 72. This interactive case is Polyarteritis nodosa and may be also helpful for hypertension: https://www.nejm.org/doi/full/10.1056/NEJMim c1302497?triggerTool=showImc This interactive case is Pheochromocytoma and may be also helpful for hypertension: https://www.nejm.org/doi/full/10.1056/NEJMim c0806409?triggerTool=showImc
Editor's Notes
- AHA = American Heart Association HP = Hypertension BP = Blood pressure Sys. = systolic Dias. = diastolic
- High-Yield Terms to Learn Baroreceptor reflex Primary autonomic mechanism for blood pressure homeostasis; involves sensory input from carotid sinus and aorta to the vasomotor center and output via the parasympathetic and sympathetic motor nerves Catecholamine reuptake pump (norepinephrine transporter [NET]) Nerve terminal transporter responsible for recycling norepinephrine after release into the synapse Catecholamine vesicle pump Storage vesicle transporter that pumps catecholamine from neural cytoplasm into the storage vesicle; also called vesicle monoamine transporter (VMAT) End-organ damage Vascular damage in heart, kidney, retina, or brain Essential hypertension Hypertension of unknown etiology; also called primary hypertension False transmitter Substance, for example, octopamine, stored in vesicles and released into synaptic cleft but lacking the effect of the true transmitter, norepinephrine Hypertensive emergency (“malignant hypertension”) An accelerated form of severe hypertension associated with rising blood pressure and rapidly progressing damage to vessels and end organs. Often signaled by renal damage, encephalopathy, and retinal hemorrhages or by angina, stroke, or myocardial infarction Orthostatic hypotension Hypotension on assuming upright posture; postural hypotension Postganglionic neuron blocker Drug that blocks transmission by an action in the terminals of the postganglionic nerves Rebound hypertension Elevated blood pressure (usually above pretreatment levels) resulting from loss of antihypertensive drug effect Reflex tachycardia Tachycardia resulting from lowering of blood pressure; mediated by the baroreceptor reflex Secondary hypertension Hypertension caused by a diagnosable abnormality, eg, aortic coarctation, renal artery stenosis, adrenal tumor, etc. Compare essential hypertension. Stepped care Progressive addition of drugs to an antihypertensive regimen, starting with one (usually a diuretic) and adding in stepwise fashion an angiotensin inhibitor, a sympatholytic, and a vasodilator Sympatholytic, sympathoplegic Drug that reduces effects of the sympathetic nervous system
- Compensatory responses (orange boxes) to decreased blood pressure when treating hypertension. The initial treatment that causes the compensatory responses might be a vasodilator. Arrows with minus signs indicate drugs used (white boxes) to minimize the compensatory responses. ACE, angiotensin-converting enzyme.
- Thiazides: chlorthalidone, hydrochlorothiazide
- Ganglion blockers block both parasympathetic and sympathetic ganglia. Their adverse effects are extensions of their pharmacologic effects and include: Sympathoplegia (Orthostatic hypotension, sexual dysfunction) and Parasympathoplegia (Constipation, urinary retention, glaucoma, blurred vision, dry mouth).
- Baroreceptor reflex arc and sites of action of sympathoplegic drugs. The letters (A–E) indicate potential sites of action of subgroups of sympathoplegics described in the text. No clinically useful drugs act at the baroreceptor (site A), but drugs are available for each of the other sites. Ref: katzung and trevor edition 2015
- Nebivolol (Not in Iran) has some direct vasodilator action caused by nitric oxide release.
- Aliskiren is not in Iran
- Sites of action of drugs that interfere with the renin-angiotensin-aldosterone system. ACE, angiotensin-converting enzyme; ARBs, angiotensin receptor blockers
- Treatment algorithm for adults with hypertension. Algorithm is based on recommendations of the American Heart Association and the American College of Cardiology (
- The goal is to lower blood pressure to the 140–160/90–110 mm Hg promptly (within a few hours).
- Major pathogenic components in the development of PAH. Vascular remodeling occurs as changes in the intraluminal radius with or without changes in the vascular wall thickness. Changes in intraluminal radius of small pulmonary arteries and arterioles have dramatic effects on the PVR. Pathogenic factors contributing to the development and progression of PAH include sustained vasoconstriction, pulmonary vascular remodeling, in situ thrombosis, and vascular wall stiffening.
- Clinical use of PAH drugs based on functional class. Treatment of PAH is generally based on the patient’s functional classification at the time of presentation. Four functional classes have been defined for PAH: (I) no symptoms or functional limitation; (II) slight limitation of physical activity; (III) marked limitation of physical activity; and (IV) symptoms with any activity or at rest. In patients with no functional limitation, there is no specific therapy that has shown benefit in clinical trials. Expert guidelines recommend only supportive care and physical rehabilitation in this group. Patients with symptoms consistent with functional classes II and III have the best evidence for therapeutic benefits. First-line therapeutics include oral agents such as ERAs, PDE5 inhibitors, sGC stimulators, and the IPR antagonist selexipag. Inhaled PGI2 analogues can also be considered. The oral formulation of treprostinil has been approved for use in minimally symptomatic individuals but should be reserved for use only as monotherapy. The most severely limited patients, those in functional class IV, or those with evidence of right heart dysfunction should be started on the most potent vasodilators, which include the intravenous and subcutaneous formulations of PGI2 analogues. Alternatively, combination therapy using multiple agents has been shown to be effective in small clinical trials and one phase 3 clinical trial combining ambrisentan and tadalafil. *approved for monotherapy only.
- Stimulators of NO/cGMP signaling. NO stimulates sGC to produce cGMP, which has vasodilating effects through decreased [Ca2+]cyt as well as anticoagulant and antiproliferative effects that are both dependent and independent of [Ca2+]cyt. cGMP is degraded primarily by PDE5 in PASMCs, which is targeted by the PDE5 inhibitors sildenafil and tadalafil.
- Isoxsuprine (used as isoxsuprine hydrochloride) is a drug used as a vasodilator in humans and equines. Isoxsuprine is a β2 adrenoreceptor agonist